Paper Information

Journal:   RAZI JOURNAL OF MEDICAL SCIENCES (JOURNAL OF IRAN UNIVERSITY OF MEDICAL SCIENCES)   MAY 2010 , Volume 17 , Number 71; Page(s) 7 To 13.
 
Paper:  SIMVASTATIN-INDUCED RENAL PROTECTION AGAINST ISCHEMIA-REPERFUSION INJURY MEDIATED BY ACTIVATION OF ATP-SENSITIVE POTASSIUM CHANNELS
 
Author(s):  ABOTALEB N.*, PAZOUKI H.R., HOMAYOONFAR H., NOURI SAMAGH J.
 
* FACULTY OF MEDICINE, IRAN UNIVERSITY OF MEDICAL SCIENCES AND HEALTH SERVICES, TEHRAN, IRAN
 
Abstract: 

Background & Aim: Renal dysfunction due to ischemia-reperfusion (I/R) injury is a common problem following renovascular surgery or kidney transplantation. There is a lot of emerging evidence that statins, which are HMG-COA reductase inhibitors, have renal protective effects against ischemia-reperfusion injury, but the exact mechanism of their protective effect has not been detected properly. This study examined whether simvastatin reduces I/R injury in kidney. In addition, we investigated whether the observed renal protective effect of simvastatin is due to the activation of ATP-sensitive potassium (KATP) channels by using selective antagonist glibenclamide. Material and Method: In this experimental study, male wistar rats(150-200 g) were randomized into five groups while their right kidneys had been removed 3 weeks prior to the study: sham operated, I/R group, I/R pretreated with simvastatin (20mg/kg/day) for 3 days by gavage, simvastatin + glibenclamide(0.3mg/kg ip) +I/R and glibenclamide +I/R. The I/R injury was induced by clamping the left renal artery for 45 minutes followed by reperfusion for 2 hours. For statistical comparison,one-way ANOVA, Mann-Whitney test and Tukey were used and p<0.05 and p<0.01 were considered significant.
Results: In I/R group, the level of both BUN and creatinin, as indices of renal cell damage, were significantly increased compared with the sham-operated group. However, these increases were significantly inhibited by the treatment with simvastatin. Simvastatin also improved the renal histological damage compared with the IR group (p<0.05). Glibenclamide, the KATP channel inhibitor, significantly decreased the protective effect of simvastatin (p<0.01).
Conclusion: Simvastatin, as an HMG-COA reductase inhibitor, has renal protective effects against ischemia-reperfusion injury independent of its lipid–lowering properties.This protective effect is mediated via activation of the adenosine triphosphate-sensitive potassium channels, and glibenclamide as a KATP channel inhibitor reduces this benefical effect of simvastatin.

 
Keyword(s): ISCHEMIA-REPERFUSION, ATP-SENSITIVE POTASSIUM CHANNEL, SIMVASTATIN, KIDNEY
 
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